The role of CD147 in ischemic inflammation and brain injury

CD147在缺血性炎症和脑损伤中的作用

基本信息

  • 批准号:
    8877660
  • 负责人:
  • 金额:
    $ 31.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-08-01 至 2016-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This R01 application aims to investigate novel roles of CD147 in stroke-induced peripheral immune dysfunction and stroke pathology. Recent studies, including our own, favor an important notion that stroke-induced peripheral immune dysfunction not only predisposes patients to post-stroke infections (particularly pneumonia) but also contributes to secondary brain damage by exacerbating and perpetuating inflammatory response in the post-ischemic brain. The spleen has emerged as a novel target that mediates the peripheral immune response after stroke. Based on the novel findings discussed in the Preliminary Studies section, we propose the central hypothesis that CD147 acts as a novel key regulator of the splenic response to focal cerebral ischemia and that contributes importantly to secondary brain damage after stroke. Specifically, we propose that spleen monocytes play a critical role in stroke- mediated brain injury through a novel CD147 mechanism. Specific Aim 1 will test the hypothesis that CD147 contributes importantly to ischemic inflammation and brain injury and thus therapeutic blockade of CD147 provides neurovascular protection in ischemic stroke. Aim 1a: We will investigate whether therapeutic targeting of CD147 provides neurovascular protection in ischemic stroke. Anti-CD147 function-blocking antibodies will be given by intravenous injection at clinically relevant time points. Aim 1b: We will investigate the cellular and molecular mechanisms by which CD147 contributes to stroke injury, with a focus on examining brain leukocyte infiltration, BBB disruption, and the splenic inflammatory activation after stroke. Aim 1c: We will determine whether therapeutic targeting of CD147 has long-term beneficial effects on functional recovery after stroke. Specific Aim 2 will test the hypothesis tha CD147 is a key mediator of the spleen's immune response and contribution to ischemic stroke through spleen inflammatory monocytes. Aim 2a: We will determine the cell-type specific expression of CD147 in the spleens of mice subjected to tMCAO and the role of CD147 in inflammatory activation of splenic immunocytes (particularly monocytes, T cells) after stroke. Aim 2b: By adoptive transfer of spleen monocytes into splenectomized mice, we will determine whether spleen inflammatory monocytes contribute importantly to stroke injury. To selectively target CD147 on spleen monocytes, siRNA knockdown technique will be used. Aim 2c: We will determine the effects of therapeutic targeting of CD147 on stroke-induced splenic atrophy and poststroke infections. These studies will reveal novel roles of CD147 in the spleen's immune response and contribution to cerebral ischemia, and the findings may have potential implications for developing novel treatments for stroke.
描述(由申请人提供):本R01申请旨在研究CD147在卒中诱导的外周免疫功能障碍和卒中病理中的新作用。最近的研究,包括我们自己的研究,支持一个重要的概念,即中风引起的外周免疫功能障碍不仅使患者易患中风后感染(特别是肺炎),而且还通过加剧和延续缺血后大脑的炎症反应,导致继发性脑损伤。脾已成为中风后调节外周免疫反应的新靶点。基于在“初步研究”部分中讨论的新发现,我们提出了CD147作为局灶性脑缺血脾反应的一种新的关键调节因子,并在脑卒中后继发性脑损伤中起重要作用的中心假设。具体来说,我们提出脾脏单核细胞通过一种新的CD147机制在脑卒中介导的脑损伤中发挥关键作用。特异性目的1将验证CD147在缺血性炎症和脑损伤中起重要作用的假设,因此治疗性阻断CD147可在缺血性卒中中提供神经血管保护。目的1a:我们将研究靶向治疗CD147是否在缺血性卒中中提供神经血管保护。在临床相关时间点静脉注射抗cd147功能阻断抗体。目的1b:我们将研究CD147促进脑卒中损伤的细胞和分子机制,重点研究脑卒中后脑白细胞浸润、血脑屏障破坏和脾炎症激活。目的1c:我们将确定靶向治疗CD147是否对脑卒中后功能恢复有长期的有益影响。特异性目的2将验证CD147是脾脏免疫反应的关键介质,并通过脾脏炎症单核细胞参与缺血性卒中。目的2a:我们将测定经tMCAO处理的小鼠脾脏中CD147的细胞类型特异性表达,以及CD147在中风后脾免疫细胞(特别是单核细胞、T细胞)炎症激活中的作用。目的2b:通过脾单核细胞过继移植脾切除小鼠,我们将确定脾炎性单核细胞是否在脑卒中损伤中起重要作用。为了选择性地靶向脾脏单核细胞上的CD147,将使用siRNA敲低技术。目的2c:我们将确定靶向治疗CD147对脑卒中诱导的脾萎缩和脑卒中后感染的影响。这些研究将揭示CD147在脾脏免疫反应和脑缺血中的新作用,这些发现可能对开发新的中风治疗方法具有潜在的意义。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Guohong Li其他文献

Guohong Li的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Guohong Li', 18)}}的其他基金

A New Molecular Target to Enhance Poststroke Cognitive Recovery
增强中风后认知恢复的新分子靶点
  • 批准号:
    10658539
  • 财政年份:
    2023
  • 资助金额:
    $ 31.72万
  • 项目类别:
Novel Targets and Therapeutic Interventions against Cerebral Ischemia-Reperfusion Injury
脑缺血再灌注损伤的新靶点和治疗干预措施
  • 批准号:
    10297340
  • 财政年份:
    2021
  • 资助金额:
    $ 31.72万
  • 项目类别:
Novel Targets and Therapeutic Interventions against Cerebral Ischemia-Reperfusion Injury
脑缺血再灌注损伤的新靶点和治疗干预措施
  • 批准号:
    10624293
  • 财政年份:
    2021
  • 资助金额:
    $ 31.72万
  • 项目类别:
Novel Targets and Therapeutic Interventions against Cerebral Ischemia-Reperfusion Injury
脑缺血再灌注损伤的新靶点和治疗干预措施
  • 批准号:
    10414999
  • 财政年份:
    2021
  • 资助金额:
    $ 31.72万
  • 项目类别:
Therapeutic Targeting of the Class IB PI3-Kinase Gamma for Treatment of Acute Ischemic Stroke
IB 类 PI3 激酶 Gamma 的治疗靶向治疗急性缺血性中风
  • 批准号:
    9344701
  • 财政年份:
    2016
  • 资助金额:
    $ 31.72万
  • 项目类别:
Therapeutic Targeting of the Class IB PI3-Kinase Gamma for Treatment of Acute Ischemic Stroke
IB 类 PI3 激酶 Gamma 的治疗靶向治疗急性缺血性中风
  • 批准号:
    9318030
  • 财政年份:
    2016
  • 资助金额:
    $ 31.72万
  • 项目类别:
The Role of CD147 in Ischemic Inflammation and Brain Injury
CD147 在缺血性炎症和脑损伤中的作用
  • 批准号:
    9348678
  • 财政年份:
    2016
  • 资助金额:
    $ 31.72万
  • 项目类别:
The role of CD147 in ischemic inflammation and brain injury
CD147在缺血性炎症和脑损伤中的作用
  • 批准号:
    8767043
  • 财政年份:
    2014
  • 资助金额:
    $ 31.72万
  • 项目类别:
Mechanisms of CD40/CD40L in vascular injury and repair
CD40/CD40L在血管损伤与修复中的机制
  • 批准号:
    7527030
  • 财政年份:
    2008
  • 资助金额:
    $ 31.72万
  • 项目类别:
Mechanisms of CD40/CD40L in vascular injury and repair
CD40/CD40L在血管损伤与修复中的机制
  • 批准号:
    7910679
  • 财政年份:
    2008
  • 资助金额:
    $ 31.72万
  • 项目类别:

相似海外基金

Non-invasive coronary thrombus imaging to define the cause of acute myocardial infarction
无创冠状动脉血栓显像可明确急性心肌梗塞的病因
  • 批准号:
    MR/Y009770/1
  • 财政年份:
    2023
  • 资助金额:
    $ 31.72万
  • 项目类别:
    Fellowship
Impact of COVID-19 pandemic on pathophysiology of acute myocardial infarction and emergency cardiovascular care system
COVID-19大流行对急性心肌梗死病理生理学和心血管急诊系统的影响
  • 批准号:
    23K15160
  • 财政年份:
    2023
  • 资助金额:
    $ 31.72万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Extreme Heat and Acute Myocardial Infarction: Effect Modifications by Sex, Medical History, and Air Pollution
酷热和急性心肌梗塞:性别、病史和空气污染的影响
  • 批准号:
    10709134
  • 财政年份:
    2023
  • 资助金额:
    $ 31.72万
  • 项目类别:
Development of a multi-RNA signature in blood towards a rapid diagnostic test to robustly distinguish patients with acute myocardial infarction
开发血液中的多 RNA 特征以进行快速诊断测试,以强有力地区分急性心肌梗死患者
  • 批准号:
    10603548
  • 财政年份:
    2023
  • 资助金额:
    $ 31.72万
  • 项目类别:
Effectiveness of Strategies to Improve Outcomes after Hospitalization for Acute Myocardial Infarction in Older Adults
改善老年人急性心肌梗死住院后预后的策略的有效性
  • 批准号:
    10576349
  • 财政年份:
    2022
  • 资助金额:
    $ 31.72万
  • 项目类别:
Establishment of the emergency transport decision making program for patients with acute myocardial infarction using artificial intelligence (AI)
利用人工智能(AI)建立急性心肌梗死患者紧急转运决策方案
  • 批准号:
    22K09185
  • 财政年份:
    2022
  • 资助金额:
    $ 31.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Developing Federated Learning Strategies for Disease Surveillance Using Cross-Jurisdiction Electronic Medical Records without Data Sharing: With Applications to Acute Myocardial Infarction, Hypertension, and Sepsis Detection
使用跨辖区电子病历(无需数据共享)开发疾病监测联合学习策略:在急性心肌梗塞、高血压和脓毒症检测中的应用
  • 批准号:
    468573
  • 财政年份:
    2022
  • 资助金额:
    $ 31.72万
  • 项目类别:
    Operating Grants
Evaluation of effect of intracoronary supersaturated oxygen therapy on inhibition of no reflow phenomenon in acute myocardial infarction
冠状动脉内过饱和氧治疗抑制急性心肌梗死无复流现象的效果评价
  • 批准号:
    22K08135
  • 财政年份:
    2022
  • 资助金额:
    $ 31.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Effectiveness of Strategies to Improve Outcomes after Hospitalization for Acute Myocardial Infarction in Older Adults
改善老年人急性心肌梗死住院后预后的策略的有效性
  • 批准号:
    10339915
  • 财政年份:
    2022
  • 资助金额:
    $ 31.72万
  • 项目类别:
The Personalising Acute Myocardial Infarction Care to improve Outcomes (PAMICO Project)
个性化急性心肌梗死护理以改善结果(PAMICO 项目)
  • 批准号:
    nhmrc : 2005797
  • 财政年份:
    2021
  • 资助金额:
    $ 31.72万
  • 项目类别:
    Partnership Projects
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了